Structure basis for C-C chemokine receptor 4 modulation by orthosteric and allosteric antagonists - PubMed
2 days ago
- #chemokine receptors
- #CCR4
- #structural biology
- CCR4 is a therapeutic target validated for cancers like adult T-cell leukemia and cutaneous T-cell lymphoma.
- Structures reveal two clinical-stage drugs (Tivumecirnon, Zelnecirnon) bind the orthosteric site, blocking chemokine recognition.
- Two other inhibitors (AZD2098, GSK2239633A) bind an allosteric site near TM7-H8, likely interfering with G-protein coupling.
- The antibody mogamulizumab binds CCR4's N-terminal region without competing with CCL17, acting via antibody-dependent cellular cytotoxicity.
- These findings provide a framework for designing next-generation chemokine receptor-targeted therapies.